What are the other Names for this Condition? (Also known as/Synonyms)

• 11q Duplication Syndrome
• Partial Trisomy 11q Syndrome
• Trisomy 11q Syndrome

What is Chromosome 11q Duplication Syndrome? (Definition/Background Information)

• Chromosome 11q Duplication Syndrome is a rare genetic disorder, in which the end of the long arm of chromosome 11 (11q) is duplicated, such that the affected individual has 3 copies of this region in every cell of his or her body, as against the normal 2 copies
• The disorder is characterized by intra-uterine growth retardation, craniofacial abnormalities, and mental retardation, as well as skeletal and reproductive organ abnormalities. Chromosome 11q Duplication Syndrome can occur spontaneously, or as a result of translocation of 11q region with another chromosome (in most cases, chromosome 22q)
• Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of the body systems. The treatment may involve physician experts from several specialties, and can include physiotherapy and surgery for correction of physical defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 11q Duplication Syndrome are able to cope well through adequate treatment and supportive care. Some of the signs and symptoms associated with the condition are known to improve with time

Who gets Chromosome 11q Duplication Syndrome? (Age and Sex Distribution)

• Chromosome 11q Duplication Syndrome is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• In many cases, individuals with mild signs and symptoms may be undiagnosed in their lifetime. Hence, a true incidence of the disorder may be difficult to estimate
• Both males and females may be affected, although the disorder is more common in females
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Chromosome 11q Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 11q Duplication Syndrome.

• Having a parent with a balanced translocation involving chromosome 11q may be an important risk factor for 11q Duplication Syndrome in the next generation (positive family history)
• Currently, no environmental and lifestyle (including dietary) factors have been implicated
• The syndrome is not caused by what the expectant mother does or does not do, either prior to or during pregnancy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chromosome 11q Duplication Syndrome? (Etiology)

Chromosome 11q Duplication Syndrome can be caused by translocation of genetic material between chromosome 11q end and another chromosome, generally chromosome 22q terminus.

• This translocation can occur sporadically, resulting in a set of chromosomes that is different from the one an individual is born with
• If this re-arrangement does not result in a net gain or loss of genetic material, it is known as a “balanced translocation”
• Those with balanced translocation of 11q can have abnormalities in the development of egg or sperm, resulting in 11q Duplication Syndrome in the offspring
• There are two chromosomes numbered 11. Children with 11q Duplication Syndrome typically will have one (chromosome 11) in normal condition, while the other is abnormal. The abnormality is characterized by a gain of chromosomal material
• It is observed that when the duplication of material occurs at the tip of the chromosome, the conditions are generally mild. In severe cases, where large duplications are noted (or the centromere, present in the middle portion of the chromosome, is involved), the child may be severely affected

It is important to note that a child’s development and future is not only influenced by the chromosome material duplicated/deleted and genes involved, but also by other factors such as one’s environment, involvement of other genes, and unique personality.

Additional (general) information on chromosomes, which is helpful in understanding the disorder:

Chromosomes are microscopic thread-like protein structures present in each cell nucleus that carry genetic information in the form of DNA (deoxyribonucleic acid). DNAs are nucleic acids that encodes the genetic information of any organisms; a basic unit of the DNA is termed a gene with a specific set of instructions and a defined function. Each chromosome is “X” shaped with a center, called the centromere, and two short arms (termed p arms) and two long arms (termed q arms).

Humans have 46 chromosomes in the cell nucleus, in 23 pairs, of which one pair is named the sex chromosome. In males, it is designated XY, for chromosome X and chromosome Y; while, in females, it is designated XX, for a pair of chromosome X. The other 22 pairs of chromosomes are numbered chromosome 1 through 22, approximately according to size (with chromosome 1 being the largest; chromosome 21 being the smallest) and are referred to as autosomes or somatic chromosomes. During conception, the embryo inherits one copy of each chromosome from each parent (i.e., mother and father). Any alteration in the chromosome numbers or structure, such as via addition or deletion of chromosomal material, can result in mild to severe genetic abnormalities that may manifest as birth defects, growth delays, and intellectual disabilities.

A chromosome duplication disorder indicates that a certain portion of the chromosomal material is duplicated, which may be detected through molecular genetic testing. Depending on the nature and amount of extra material, the manifestation of a set of signs and symptoms are noted.

What are the Signs and Symptoms of Chromosome 11q Duplication Syndrome?

The signs and symptoms of Chromosome 11q Duplication Syndrome may be significantly different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material added and the number of genes affected. As a general rule, a small gain in chromosome material generally results in milder signs and symptoms. Conversely, larger gains/duplications of the chromosome material generally results in severe signs and symptoms. It is important to note that exceptions may also occur, where individuals with small amount of chromosomal gains, may have disproportionately severe presentations.

The associated signs and symptoms depend on what material is duplicated, how much duplication has occurred (quantity), where the duplications occurs (such as at the tip or center of the chromosome), and if the involvement of another chromosome is noted (known to occur in some cases).

The commonly noted signs and symptoms of 11q Duplication Syndrome include:

• Craniofacial abnormalities
  • Small head (microcephaly)
  • Short and broad head (brachycephaly)
  • Low set ears, with or without preauricular pits/tags
  • Widely spaced eyes
  • Downward slanting eyes
  • Epicanthal folds
  • Short nose
  • Cleft palate
  • Abnormally long vertical groove at center of upper lip
• Skeletal abnormalities
  • Collarbone malformation
  • Abnormal hip structure
  • Hip dislocation
• Movement disorders
• Loose skin
• Structural abnormalities of the heart
• Under-development of corpus callosum (the layer that divides the two halves of the brain)
• Mild to moderate mental retardation
• Genital abnormalities in males such as:
  • Undescended testes
  • Small penis

How is Chromosome 11q Duplication Diagnosed Syndrome?

Children can have varying signs and symptoms. Some children with mild signs and symptoms may go undiagnosed in their lifetimes. Given the rarity of the condition, the healthcare provider should have a high index of suspicion to consider Chromosome 11q Duplication Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

11q Duplication Syndrome is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms, including evaluation of body systems such as vision, hearing, muscles, heart, kidneys, central nervous system, genitalia, and immune system
• Hearing and vision assessment through various tests
• Evaluation of heart defects through:
  • Chest X-rays
  • Echocardiogram
  • Electrocardiogram (EKG)
  • Cardiac catheterization
  • Fetal ultrasound for heart defects
• Laboratory tests, as needed, such as electrolyte levels, serum calcium levels, thyroid function test, kidney function test, urine tests, sex hormone studies, etc.
• Radiological studies of the affected regions, as needed
• Brain scans (to determine corpus callosum): These may include prenatal ultrasounds and MRI scans, and CT/MRI scans after development of the child
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Behavioral studies
• Prenatal studies including abdominal ultrasonography
• Specialized genetic testing techniques are often required to confirm the diagnosis. This may include:
  • Fluorescence in situ hybridization (FISH) testing
  • Array comparative genomic hybridization (array-CGH)
  • DNA sequencing

Often, karyotyping of the chromosome is not adequate to diagnose the condition, since individuals with this condition can have normal karyotype chromosomal studies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chromosome 11q Duplication Syndrome?

The complications of Chromosome 11q Duplication Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR)
• Psychomotor retardation affecting coordinated movement and thinking process 
• Inability to live independently
• Arrhythmias
• Heart attack
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Chromosome 11q Duplication Syndrome Treated?

There is no cure for Chromosome 11q Duplication Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. It also depends on the severity of the signs and symptoms and the body systems affected. Individuals with mild signs and symptoms may require periodic monitoring without significant medical intervention. Often, a multidisciplinary team of specialists including pediatricians, ophthalmologists, otolaryngologists, neurologists, internists, cardiologists, endocrinologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for 11q Duplication Syndrome may involve:

• Physiotherapy for weakened muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, hydrotherapy, and other adapted activities; use of specially-designed toys and daily-used items (such as spoons and cups)
• Use of hearing aids
• Employing learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition. Writing by holding a pencil may be very difficult; but touchscreen computers and keyboards are known to be easier to use and learn
• Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
• Use of walking aids including foot orthotics and special footwear and shoe inserts; wheelchair assistance may be necessary
• For feeding difficulties, use of feeding tubes (temporary nasogastric or gastrostomy tubes), medications, feed thickeners, bottle-feeding expressed milk, including special diets and nutritional supplements
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time without any invasive procedures
• Surgical correction of physical defects, as assessed by a healthcare expert
• Use of suitable glasses and surgical rectification of vision defects, if necessary
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can Chromosome 11q Duplication Syndrome be Prevented?

Chromosome 11q Duplication Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

In some rare cases, the condition may be familial, meaning they occur within families. In expecting parents with a familial history:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

It is important to note that the chances of both the parents with normal chromosomes having another child with Chromosome 11q Duplication Syndrome is highly unlikely. This may be confirmed via specialized prenatal testing and preimplantation genetic diagnosis (PGD), if needed. Prenatal tests may include chorionic villus sampling (CVS) and amniocentesis.

What is the Prognosis of Chromosome 11q Duplication Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 11q Duplication Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis
• Some children may require lifelong medical support and care

Additional and Relevant Useful Information for Chromosome 11q Duplication Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/